Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy

Nat Rev Immunol. 2022 Feb;22(2):85-96. doi: 10.1038/s41577-021-00547-6. Epub 2021 May 17.


A paradigm shift has recently occurred in the field of cancer therapeutics. Traditional anticancer agents, such as chemotherapy, radiotherapy and small-molecule drugs targeting specific signalling pathways, have been joined by cellular immunotherapies based on T cell engineering. The rapid adoption of novel, patient-specific cellular therapies builds on scientific developments in tumour immunology, genetic engineering and cell manufacturing, best illustrated by the curative potential of chimeric antigen receptor (CAR) T cell therapy targeting CD19-expressing malignancies. However, the clinical benefit observed in many patients may come at a cost. In up to one-third of patients, significant toxicities occur that are directly associated with the induction of powerful immune effector responses. The most frequently observed immune-mediated toxicities are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. This Review discusses our current understanding of their pathophysiology and clinical features, as well as the development of novel therapeutics for their prevention and/or management.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD19
  • Cytokine Release Syndrome / etiology
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy, Adoptive / adverse effects
  • Neoplasms* / drug therapy
  • Neurotoxicity Syndromes* / drug therapy
  • Neurotoxicity Syndromes* / etiology
  • Receptors, Antigen, T-Cell / genetics


  • Antigens, CD19
  • Receptors, Antigen, T-Cell